Infections from antibiotic‐resistant Staphylococcus aureus and Pseudomonas aeruginosa are a serious threat because reduced antibiotic efficacy complicates treatment decisions and prolongs the disease state in many patients. To expand the arsenal of treatments against antimicrobial‐resistant (AMR) pathogens, 600‐Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate β‐lactam antibiotics against Gram‐positive bacteria. BPEI binds cell‐wall teichoic acids and disables resistance factors from penicillin binding proteins PBP2a and PBP4. This study describes a new mechanism of action for BPEI potentiation of antibiotics generally regarded as agents effective against Gram‐positive pathogens but not Gram‐negative bacteria. 600‐Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non‐β‐lactam co‐drug, erythromycin, which targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL‐8 by human epithelial keratinocytes. This enables BPEI to function as a broad‐spectrum antibiotic potentiator, and expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care.

中文翻译：

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扩大能够杀死耐多药金黄色葡萄球菌和铜绿假单胞菌的抗生素谱。

耐抗生素金黄色葡萄球菌和铜绿假单胞菌感染是一个严重的威胁，因为降低的抗生素功效使治疗决策复杂化并延长了许多患者的疾病状态。为了扩大抗微生物（AMR）病原体的治疗范围，600-Da支链聚乙烯亚胺（BPEI）可以克服抗生素耐药机制并增强β-内酰胺抗生素对革兰氏阳性菌的作用。BPEI 结合细胞壁磷壁酸并使青霉素结合蛋白 PBP2a 和 PBP4 的抗性因子失效。这项研究描述了抗生素的 BPEI 增强作用的新机制，抗生素通常被认为是有效对抗革兰氏阳性病原体但对革兰氏阴性菌无效的药物。600-Da BPEI 能够减少药物流入的障碍并促进非β-内酰胺联合药物红霉素的吸收，红霉素靶向细胞内机制。还，BPEI 可以抑制人上皮角质形成细胞产生细胞因子白细胞介素 IL-8。这使 BPEI 能够作为广谱抗生素增效剂发挥作用，并扩大了改进药物设计、抗生素开发和针对病原菌的治疗方法的机会，尤其是在伤口护理方面。